US5698399A - Detecting genetic predisposition for osteoporosis - Google Patents

Detecting genetic predisposition for osteoporosis Download PDF

Info

Publication number
US5698399A
US5698399A US08/628,282 US62828296A US5698399A US 5698399 A US5698399 A US 5698399A US 62828296 A US62828296 A US 62828296A US 5698399 A US5698399 A US 5698399A
Authority
US
United States
Prior art keywords
osteoporosis
bone
allele
gene
genetic
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
US08/628,282
Other languages
English (en)
Inventor
Gordon W. Duff
Graham Russell
Richard Eastell
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Interleukin Genetics Inc
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to US08/628,282 priority Critical patent/US5698399A/en
Application filed by Individual filed Critical Individual
Priority to IL12280897A priority patent/IL122808A/xx
Priority to PCT/US1997/005626 priority patent/WO1997038135A1/en
Priority to EP97917861A priority patent/EP0832298B1/de
Priority to CNB97190653XA priority patent/CN100347313C/zh
Priority to AU26077/97A priority patent/AU712461B2/en
Priority to ES97917861T priority patent/ES2208892T3/es
Priority to NZ329530A priority patent/NZ329530A/en
Priority to CA002226223A priority patent/CA2226223C/en
Priority to AT97917861T priority patent/ATE247718T1/de
Priority to DE69724209T priority patent/DE69724209T2/de
Priority to ZA972909A priority patent/ZA972909B/xx
Assigned to MEDICAL SCIENCE SYSTEMS, INC. reassignment MEDICAL SCIENCE SYSTEMS, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: SHEFFIELD, UNIVERSITY OF THE
Application granted granted Critical
Publication of US5698399A publication Critical patent/US5698399A/en
Priority to MX9800192A priority patent/MX9800192A/es
Assigned to SHEFFIELD, UNIVERSITY OF, THE reassignment SHEFFIELD, UNIVERSITY OF, THE ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: DUFF, GORDON W., EASTELL, RICHARD, RUSSELL, GRAHAM
Assigned to INTERLEUKIN GENETICS, INC. reassignment INTERLEUKIN GENETICS, INC. CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). Assignors: MEDICAL SCIENCE SYSTEMS, INC
Assigned to PYXIS INNOVATIONS INC. reassignment PYXIS INNOVATIONS INC. SECURITY AGREEMENT Assignors: INTERLEUKIN GENETICS, INC.
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/156—Polymorphic or mutational markers

Definitions

  • This invention relates to a method of detecting a predisposition for osteoporosis.
  • osteoporosis was identified as "one of the leading diseases of women" by Bernadine Healy, MD, then director of the National Institutes of Health. Complications following osteoporosis fractures are the fourth leading cause of death for women over the age of 65, following heart disease, cancer and stroke. It is the leading cause of disability in the United States and the most common cause of hip fracture.
  • Type 1 osteoporosis which is postmenopausal osteoporosis stemming from loss of estrogen, affects more than half of all women over 65 and has been detected in as many as 90 percent of women over age 75.
  • Type II or senile osteoporosis which is strictly age related, affects both men and women usually over the age of seventy.
  • Another form of osteoporosis affecting both sexes is drug-induced, for example, by long-term steroid therapy, known to accelerate bone loss (Eastell, 1995).
  • Patient groups that receive long term steroid therapy include asthmatics (7 million over the age of 18 in the United States) as well as patients with rheumatoid arthritis or other autoimmune diseases. Osteoporosis can also occur in association with an underlying disease such as rheumatoid arthritis (prevalence of 1-2% in the population).
  • Osteoporosis can be diagnosed, monitored and treated with a variety of methods such as set forth in Patent applications WO9420615, WO9501995 and WO9414844 and see in general "Osteoporosis: Etiology, Diagnosis, and Management" (Raven Press, 1988).
  • Osteoporosis is responsible for a majority of the 1.5 million bone fractures each year leading to disabilities costing 10 billion dollars in medical, social, and nursing-home costs. Even in the best of hands, up to 40% of patients 65 years of age or older will not survive two years following a hip fracture.
  • Lifestyle can be a factor in onset of osteoporosis and in particular can be an important factor in building and maintaining healthy bone mass to prevent osteoporosis.
  • persons under 65 are more likely than their parents to have had a sedentary lifestyle, bad eating habits, increased alcohol and caffeine intake, and a history of greater medication associated with bone loss.
  • HRT Hormone replacement therapy
  • a method for predicting low bone mineral density (BMD) and the rate of bone density loss and thereby a susceptibility to osteoporosis includes the steps of isolating DNA from a subject and determining the DNA polymorphism pattern of the gene (IL-1RN) that codes for IL-1 receptor antagonist (IL-1ra). The pattern is then analyzed and individuals expressing a genetic polymorphism pattern at IL-1RN which is over-represented in osteoporosis populations is identified. Individuals so identified can then be treated more aggressively to prevent or retard the occurrence of disease.
  • IL-1RN DNA polymorphism pattern of the gene
  • IL-1ra IL-1 receptor antagonist
  • the present invention further discloses a kit for the identification of a subject's genetic polymorphism pattern associated with osteoporosis.
  • the kit includes DNA sample collecting means and means for determining a genetic polymorphism pattern, which is then analyzed to determine a subject's susceptibility to osteoporosis. Control samples are also included.
  • an allele of the gene (IL-1RN) for IL-1 receptor antagonist (IL-1ra) was found to be associated with osteoporosis.
  • the invention allows individuals with or without overt disease to be identified who have a genetic predisposition for osteoporosis by detecting the presence of a DNA polymorphism in the gene sequence (IL-1RN) for IL-1ra.
  • Osteoporosis is defined as set forth herein above and further as set forth in "Osteoporosis: Etiology, Diagnosis, and Management” (Raven Press, 1988), as well as Peel and Eastell (1994, 1995) and Eastell and Riggs (1988, 1987a,b).
  • osteoporosis is a bone disorder characterized by increased brittleness due to a reduction in bone density.
  • IL-1RN allele 2 An allele associated with a reduction in bone density was identified as IL-1RN allele 2 as set forth in the Example herein below. Therefore the method of the present invention identifies carriers of at least one copy of the DNA genetic polymorphism pattern associated with disease risk, IL-1RN allele 2.
  • the method of the present invention also provides for identifying individuals expressing a multiple genetic polymorphism pattern associated with risk of osteoporosis and who would therefore have an increased risk of osteoporosis.
  • the method provides for isolating genomic DNA from a subject and identifying in the DNA a genetic polymorphism pattern for the IL-1 receptor antagonist (IL-1RN) gene.
  • the DNA is then scanned for a genetic polymorphism pattern for other genes associated with osteoporosis as set forth in patents EP93113604, WO8808457, WO9311149 and WO9403633.
  • Control DNA patterns are run concurrently to allow proper identification of the polymorphism pattern. From this is determined the number of polymorphisms carried by the subject that are associated with osteoporosis risk. This allows a determination of the overall risk factor for osteoporosis.
  • Polymorphism as used herein refers to variants in the gene sequence.
  • the polymorphisms can be those variations (DNA sequence differences) which are generally found between individuals or different ethnic groups and geographic locations which, while having a different sequence, produce functionally equivalent gene products.
  • Polymorphisms also encompass variations which can be classified as alleles and/or mutations which can produce gene products which may have an altered function, i.e. variants in the sequence which can lead to gene products that are not functionally equivalent.
  • Polymorphisms also encompass variations which can be classified as alleles and/or mutations which either produce no gene product, an inactive gene product or increased gene product. Further, the term is also used interchangeably with allele as appropriate.
  • Genetic testing is carried out in general as set forth in U.S. Pat. Nos. 4,582,788, 5,110,920 and 5,387,506 for diseases associated with, or caused by, one to two genes, once the genes are identified, to determine the risk of disease for a person carrying a given gene or combination of genes (see for example U.S. Pat. Nos. 4,801,531, 4,666,828 and 5,268,267) and as set forth in the Example herein below.
  • kits for the identification of a subject's genetic polymorphism pattern associated with the risk of osteoporosis includes DNA sample collecting means and means for determining a genetic polymorphism pattern for IL-1RN. Control DNA samples which show known IL-1RN patterns can be included. Once the individual's pattern is identified, the individual's susceptibility to osteoporosis can be determined.
  • the DNA sample is obtained from blood or tissue samples.
  • the DNA will be obtained from blood cells obtained from a finger prick of the individual with the blood collected on absorbent paper.
  • the blood will be collected on an AmpliCardTM (University of Sheffield, Section of Molecular Medicine, Department of Medicine and Pharmacology, Royal Hallamshire Hospital, Sheffield, England S10 2JF).
  • Target sequences in the DNA of the dried blood spots are amplified using the polymerase chain reaction (PCR).
  • Oligonucleotide DNA primers that target the specific polymorphic DNA region within the genes of interest are prepared so that in the PCR reaction amplification of the target sequences is achieved.
  • This embodiment has the advantage of requiring only a small amount of blood and avoids the necessity for venipuncture or a tissue biopsy. Moreover, one dried blood spot can provide enough template DNA for multiple testing, allowing replication of results and testing of multiple loci. However, other means for collecting DNA and determining polymorphism patterns as known in the art can be used.
  • the amplified DNA sequences from the template DNA are then analyzed to determine the genetic polymorphisms present in the amplified sequences and thereby provide a genetic polymorphism profile of the individual.
  • Control DNA samples of the target DNA polymorphism can be run concurrently.
  • Cytokines are peptide signalling molecules that are produced by a wide range of activated cells including activated immune cells such as thymus-derived T lymphocytes (T-cells), B lymphocytes and monocyte/macrophages.
  • the cytokines include interleukins (IL-1 through IL-17), colony stimulating factors (CSFs) for granulocytes and/or macrophages (CSF-G, CSF-M, CSF-GM), tumor necrosis factors (TNFs ⁇ & ⁇ ), and interferons (IFN ⁇ , ⁇ & ⁇ ).
  • the basic activity of IL-1 includes the combined activities of IL-1 ⁇ , IL-1 ⁇ and IL-1 receptor antagonist (IL-1ra).
  • IL-1ra IL-1 receptor antagonist
  • Association of a single cytokine polymorphism and disease states have been found as, for example, in Systemic Lupus Erythematosus (Blakemore et al., 1994), Ulcerative Colitis (Mansfield et al., 1994), juvenile rheumatoid arthritis (McDowell et al., 1995) and cerebral malaria (McGuire et al., 1994).
  • Cytokines have been shown to have a role in bone remodeling. In mice it was shown that IL-6 is a mediator of bone loss due to loss of estrogen (Poli, 1994). Additionally, IL-1 and tumor necrosis factor (TNF) are involved in the regulation of bone remodeling (Mundy, 1993; Rickard et al., 1993; Matfin, 1993).
  • IL-1RN allele 2 A specific polymorphism in DNA sequences coding for IL-1ra was found to be associated with osteoporosis: IL-1RN allele 2. Alleles of this polymorphism site for the gene (IL-1RN) encoding IL-1ra are as follows Tarlow et al., "Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat" Human Genetics 91:403-404 (1993).
  • Allele 1 contains four repeats and is 412 bp;
  • Allele 2 contains two repeats and is 240 bp;
  • Allele 3 contains three repeats and is 326 bp;
  • Allele 4 contains five repeats and is 498 bp;
  • Allele 5 contains six repeats and is 584 bp.
  • the individual's polymorphism profile i.e., allelic type, is then analyzed as set forth in the present invention. Population studies have determined the expected profiles of healthy people and individuals with osteoporosis as determined by the present invention. The individual's polymorphism profile is then matched to the expected profiles and the match determines the predisposition towards osteoporosis.
  • An odds ratio (approximate relative risk) is derived to test the association between allelic polymorphism pattern (genotype) at the IL-1RN locus and development of disease. This provides predictive information that will be used in the clinical management of osteoporosis. A further odds ratio can be derived for genotypes in addition to IL-1RN associated with osteoporosis.
  • the present invention provides a method for treating individuals who are susceptible to osteoporosis.
  • the individuals are identified as discussed herein above by isolating genomic DNA from a subject, identifying in the DNA a genetic polymorphism pattern for IL-1 receptor antagonist (IL-1ra) gene IL-1RN, and from this identifying in a subject the presence of at least one copy of IL-1RN allele 2 gene thereby indicating susceptibility to osteoporosis. It is then contemplated that these individuals will be administered an antagonist of IL-1 (Il-1 ⁇ , IL-1 ⁇ or both).
  • IL-1ra IL-1 receptor antagonist
  • An antagonist therapy can be any drug or compound which will block the activity of IL-1.
  • the antagonist can bind to IL-1, inhibit or reduce production of IL-1 or inhibit the effects of IL-1 on cells.
  • therapies which modify cellular receptors for so that they are not receptive to IL-1 are also encompassed by the term.
  • Suitable agents for this use would include antibodies to IL-1 or an IL-1 receptor, soluble IL-1 binding proteins, the IL-1 receptor antagonist, anti-inflammatory cytokines (e.g. IL-6, IL-10, TGF ⁇ ), and small molecular weight drugs that suppress the synthesis, release or biological actions of IL-1, TNF, IL-6 and other cytokines involved in stimulating bone resorption or inhibiting bone formation.
  • the antagonists are administered and dosed in accordance with good medical practice, taking into account the clinical condition of the individual, the site and method of administration, scheduling of administration, and other factors known to medical practitioners.
  • the "effective amount" for purposes herein is thus determined by such considerations as are known in the art. The amount must be effective to achieve improvement including but not limited to maintenance of bone density mass and other indicators as are selected as appropriate measures by those skilled in the art. Other indicators can include maintained or increased bone mineral content, increased biochemical markers of bone formation and decreased biochemical markers of bone resorption.
  • the antagonist can be administered in various ways. It should be noted that the antagonist can be administered as the compound or as pharmaceutically acceptable salt and can be administered alone or as an active ingredient in combination with pharmaceutically acceptable carriers, diluents, adjuvants and vehicles.
  • the compounds can be administered orally, subcutaneously or parenterally including intravenous, intraarterial, intramuscular, intraperitoneally, and intranasal administration as well as intrathecal and infusion techniques depending on the route required by the antagonist being used as is known to those skilled in the art. Implants of the compounds are also useful.
  • the above discussion provides a factual basis for the present invention and for a kit for the identification of a subject's genetic polymorphism pattern associated with osteoporosis.
  • the identification of those at risk for disease allows preventive measures to be initiated prior to disease onset.
  • those individuals who have two or more risk factors, the susceptible genotype and life-style predispositions or other known genetic predispositions can be particularly monitored and aggressively treated since their risk of disease is unusually high.
  • the methods used with and the utility of the present invention can be shown by the following example.
  • Bone mineral density measurements were made by dual energy x-ray absorptiometry (DEXA) at the first clinic visit or study visit and were used for analysis (Peel and Eastell, 1994).
  • Bone mineral density (BMD) refers to the mineral content contained within a certain amount of bone. For example, if 1 gram of mineral per cm 2 of bone is found this gives a BMD of 1.0 g/cm 2 .
  • BMD is a measure of the strength of bones and their resistance to fracture from osteoporosis. Women who had taken hormone replacement therapy (HRT) for more than three months or who had taken oral corticosteroids were excluded.
  • HRT hormone replacement therapy
  • DNA was extracted from whole blood using a modification of the salt-out method (Nucleon IITM, Scotlab, UK).
  • PCR Amplification was undertaken as previously described by Tarlow et al. (1993). Enzymes used in PCR were from GIBCO BRL, thermocyclers were either Perkin-Elmer or Biometra.
  • Intron 2 of the IL-1RN gene contains a variable number tandem repeat (VNTR) region that gives rise to five (5) alleles which were identified as follows:
  • SCREENING PCR amplification of genomic templates followed by assessment of the size of the product after separation on agarose gels.
  • PRIMERS The following primers were produced in an ABI DNA synthesizer based on the genomic sequences:
  • Allele 1 contains four repeats and is 412 bp;
  • Allele 2 contains two repeats and is 240 bp;
  • Allele 3 contains three repeats and is 326 bp;
  • Allele 4 contains five repeats and is 498 bp;
  • Allele 5 contains six repeats and is 584 bp.
  • alleles 3, 4 and 5 are rare.
  • Bone mineral density was measured by dual emission x-ray absorptiometry (DEXA) (Eastell and Riggs, 1988) at lumbar spine (L2-L4) (LSBMD) and femoral neck (FNBMD).
  • DEXA dual emission x-ray absorptiometry
  • LSBMD lumbar spine
  • FNBMD femoral neck
  • IL-12+ refers to women who are either homozygous for allele 2 (2;2) or heterozygous (1;2)
  • IL-1RN2- refers to women who are homozygous for allele 1 (1;1). This system is treated as a two-allele system for purposes of analysis since alleles 3, 4 and 5 are rare.
  • the "Z" score deviation from an age corrected norm (mean) of bone density at a given anatomical site shows that normal controls have an average positive "Z” scores (although IL-1RN2+ had lower scores even in normals).
  • the fracture group had negative "Z" scores--that is lower bone densities for their age against the population norm.
  • IL-1RN2+ subjects had a lower mean bone density at two sites (more negative "Z” scores) than the women with fractures who were IL1RN2-.
  • the difference between IL-1RN(+) and IL-1RN(-) subjects at the two bone sites measured were statistically significant.
  • the present invention therefore provides a method of identifying subjects at risk for severe osteoporosis and low bone density to allow early treatment.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Analytical Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Immunology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Saccharide Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
US08/628,282 1996-04-05 1996-04-05 Detecting genetic predisposition for osteoporosis Expired - Lifetime US5698399A (en)

Priority Applications (13)

Application Number Priority Date Filing Date Title
US08/628,282 US5698399A (en) 1996-04-05 1996-04-05 Detecting genetic predisposition for osteoporosis
DE69724209T DE69724209T2 (de) 1996-04-05 1997-04-03 Erkennung einer genetischen prädisposition fur osteoporose
EP97917861A EP0832298B1 (de) 1996-04-05 1997-04-03 Erkennung einer genetischen prädisposition fur osteoporose
CNB97190653XA CN100347313C (zh) 1996-04-05 1997-04-03 检测骨质疏松症的遗传素因
AU26077/97A AU712461B2 (en) 1996-04-05 1997-04-03 Detecting genetic predisposition for osteoporosis
ES97917861T ES2208892T3 (es) 1996-04-05 1997-04-03 Deteccion de predisposicion genetica a la osteoporisis.
NZ329530A NZ329530A (en) 1996-04-05 1997-04-03 A method and kit for the identification of the il-1rn genetic polymorphism pattern associated with low bone mineral density in osteoporosis
CA002226223A CA2226223C (en) 1996-04-05 1997-04-03 Detecting genetic predisposition for osteoporosis
IL12280897A IL122808A (en) 1996-04-05 1997-04-03 Method for detecting genetic predisposition for osteoporosis
PCT/US1997/005626 WO1997038135A1 (en) 1996-04-05 1997-04-03 Detecting genetic predisposition for osteoporosis
AT97917861T ATE247718T1 (de) 1996-04-05 1997-04-03 Erkennung einer genetischen prädisposition fur osteoporose
ZA972909A ZA972909B (en) 1996-04-05 1997-04-04 Detecting genetic predisposition for osteoporosis
MX9800192A MX9800192A (es) 1996-04-05 1998-01-07 Deteccion de predisposicion genetica a la osteoporosis.

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US08/628,282 US5698399A (en) 1996-04-05 1996-04-05 Detecting genetic predisposition for osteoporosis

Publications (1)

Publication Number Publication Date
US5698399A true US5698399A (en) 1997-12-16

Family

ID=24518226

Family Applications (1)

Application Number Title Priority Date Filing Date
US08/628,282 Expired - Lifetime US5698399A (en) 1996-04-05 1996-04-05 Detecting genetic predisposition for osteoporosis

Country Status (13)

Country Link
US (1) US5698399A (de)
EP (1) EP0832298B1 (de)
CN (1) CN100347313C (de)
AT (1) ATE247718T1 (de)
AU (1) AU712461B2 (de)
CA (1) CA2226223C (de)
DE (1) DE69724209T2 (de)
ES (1) ES2208892T3 (de)
IL (1) IL122808A (de)
MX (1) MX9800192A (de)
NZ (1) NZ329530A (de)
WO (1) WO1997038135A1 (de)
ZA (1) ZA972909B (de)

Cited By (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998040517A1 (en) * 1997-03-10 1998-09-17 Medical Science Systems, Inc. Prediction of coronary artery disease
US5939260A (en) * 1996-04-19 1999-08-17 Gemini International Holdings Limited Methods of diagnosing a predisposition for osteoarthritis via detection of vitamin D receptor gene polymorphisms
US5998137A (en) * 1996-01-17 1999-12-07 Grainger; David J. Methods of diagnosis by detecting polymorphisms in the TGF-β1 promoter
WO2000032826A1 (en) * 1998-11-30 2000-06-08 Drexel University Methods and kits for identifying individuals at risk of developing osteoporosis
US6268142B1 (en) * 1997-05-29 2001-07-31 Interleukin Genetics, Inc. Diagnostics and therapeutics for diseases associated with an IL-1 inflammatory haplotype
US6391543B2 (en) * 1997-04-23 2002-05-21 Abbott Laboratories Reagents and methods useful for detecting diseases of the prostate
US6524795B1 (en) * 1997-03-10 2003-02-25 Interleukin Genetics, Inc. Diagnostics for cardiovascular disorders
US6558905B1 (en) * 1999-08-30 2003-05-06 Interleukin Genetics, Inc. Diagnostics and therapeutics for osteoporosis
US20030124524A1 (en) * 2000-06-23 2003-07-03 Kenneth Kornman Screening assays for identifying modulators of the inflammatory or immune response
US20030148288A1 (en) * 2002-02-01 2003-08-07 Yi-Wei Tang Colorimetric genetic test for clinically significant TNF polymorphism and methods of use thereof
US20030152947A1 (en) * 2001-06-15 2003-08-14 Crossman David C. Methods for detecting and treating the early onset of aging-related conditions
US20030198316A1 (en) * 2002-04-17 2003-10-23 Piet Dewaele Osteoporosis screening method
US20030235890A1 (en) * 2001-11-19 2003-12-25 David Wyllie Functional polymorphisms of the interleukin-1 locus affecting transcription and susceptibility to inflammatory and infectious diseases
US6713253B1 (en) 1996-10-10 2004-03-30 Interleukin Genetics, Inc. Detecting genetic predisposition to sight-threatening diabetic retinopathy
US6733967B1 (en) 1998-04-21 2004-05-11 Interleukin Genetics, Inc. Fetal testing for prediction of low birth weight
US6762023B1 (en) 1998-11-30 2004-07-13 Drexel University Methods for identifying individuals at risk of developing osteoporosis
WO2004065630A1 (en) * 2003-01-24 2004-08-05 King's College London Detection of predisposition to osteoporosis
US20040229264A1 (en) * 1997-03-10 2004-11-18 Interleukin Genetics, Inc. Diagnostics and therapeutics for restenosis
US20040229228A1 (en) * 2002-07-25 2004-11-18 Northwestern University Il-1 genotype in early kidney allograft rejection
US20050032077A1 (en) * 1998-03-10 2005-02-10 Duff Gordon W. Detecting genetic predisposition to sight-threatening diabetic retinopathy
US20050064453A1 (en) * 1999-06-30 2005-03-24 Gordon Duff Diagnostics and therapeutics for early-onset menopause
US20050084882A1 (en) * 2000-08-30 2005-04-21 Kenneth Kormman Diagnostics and therapeutics for osteoporosis
US20050221306A1 (en) * 2001-11-03 2005-10-06 Wilson Scott G Detection of predisposition to osteoporosis
US20050282198A1 (en) * 1997-05-29 2005-12-22 Interleukin Genetics, Inc. Diagnostics and therapeutics for diseases associated with an IL-1 inflammatory haplotype
US20080311581A1 (en) * 2001-11-19 2008-12-18 David Wyllie Functional polymorphisms of the interleukin-1 locus affecting transcription and susceptibility to inflammatory and infectious diseases
US20090023147A1 (en) * 1999-08-30 2009-01-22 Kenneth Kornman Diagnostics and therapeutics for osteoporosis
US20090170105A1 (en) * 2007-11-08 2009-07-02 Interleukin Genetics, Inc. Diagnostics for Aging-Related Dermatologic Disorders
US20090191564A1 (en) * 2005-11-17 2009-07-30 Sheila Francis Diagnostics and therapeutics for cardiovascular disorders
US20100098775A1 (en) * 2008-05-02 2010-04-22 Interleukin Genetics, Inc. Detecting genetic predisposition to osteoarthritis associated conditions
US20100129798A1 (en) * 2008-05-02 2010-05-27 Interleukin Genetics, Inc. Detecting genetic predisposition to osteoarthritis associated conditions
WO2017123696A1 (en) 2016-01-12 2017-07-20 Interleukin Genetics, Inc. Methods for predicting response to treatment
WO2018130670A1 (en) 2017-01-12 2018-07-19 Cardioforecast Ltd Methods and kits for treating cardiovascular disease
WO2020245402A1 (en) 2019-06-06 2020-12-10 Cardioforecast Ltd Compositions and methods for treating lung, colorectal and breast cancer
WO2021028469A1 (en) 2019-08-12 2021-02-18 Sitokine Limited Compositions and methods for treating cytokine release syndrome and neurotoxicity
WO2021205013A1 (en) 2020-04-09 2021-10-14 Sitokine Limited Compositions and methods for treating covid-19

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6203993B1 (en) 1996-08-14 2001-03-20 Exact Science Corp. Methods for the detection of nucleic acids
US6300077B1 (en) 1996-08-14 2001-10-09 Exact Sciences Corporation Methods for the detection of nucleic acids
GB9706359D0 (en) * 1997-03-27 1997-05-14 Gemini International Holdings Polymorphisms of an il-1 receptor antagonist gene
IL139131A0 (en) * 1998-04-21 2001-11-25 Interleukin Genetics Inc Fetal testing for prediction of low birth weight
EP1086247A2 (de) * 1998-06-16 2001-03-28 Exact Laboratories, Inc. Verfahren zum nachweis von nukleinsäuren
AUPP547398A0 (en) * 1998-08-26 1998-09-17 Medvet Science Pty. Ltd. Predictive assessment of certain skeletal disorders
CA2343049A1 (en) * 1998-09-15 2000-03-23 Signalgene Inc. Combination of markers at the estrogen- and vitamin d-receptor genes or equivalents thereof to prognose a response to osteoporosis therapy
WO2001078575A2 (en) * 2000-04-17 2001-10-25 Oregon Health & Science University Ext2 as a predictive marker for osteoporosis
AU2003287955B2 (en) * 2002-09-30 2007-06-21 Novartis Ag Methods to predict cholesterol elevations during immunosuppressant therapy
EP3536853A1 (de) 2018-03-06 2019-09-11 Lenzing Aktiengesellschaft Lyocellfaser mit verringerter pillenbildung

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5064851A (en) * 1990-07-24 1991-11-12 Pfizer Inc. 3-(1-substituted-pyrazoyl)-2-oxindole derivatives, compositions and use
US5593833A (en) * 1992-07-31 1997-01-14 Garvan Institute Of Medical Research Assessment of allelic variation in vitamin D receptor correlated to bone density or turnover

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1269989B (it) * 1994-09-21 1997-04-16 Dompe Spa Antagonisti recettoriali di il-1 ad aumentata attivita' inibitoria

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5064851A (en) * 1990-07-24 1991-11-12 Pfizer Inc. 3-(1-substituted-pyrazoyl)-2-oxindole derivatives, compositions and use
US5593833A (en) * 1992-07-31 1997-01-14 Garvan Institute Of Medical Research Assessment of allelic variation in vitamin D receptor correlated to bone density or turnover

Non-Patent Citations (78)

* Cited by examiner, † Cited by third party
Title
Anderson and Pollitzer, "Ethnic and genetic differences in susceptibility to osteoporotic fractures", Adv Nutr Res, 9:129-49 (1994).
Anderson and Pollitzer, Ethnic and genetic differences in susceptibility to osteoporotic fractures , Adv Nutr Res , 9:129 49 (1994). *
Basic and Clinical Immunology, 8th Ed. eds Stites, Terr & Parslow, Chapter 9 pp. 105 123. *
Basic and Clinical Immunology, 8th Ed. eds Stites, Terr & Parslow, Chapter 9 pp. 105-123.
Blakemore et al., "Interleukin-1 receptor antagonist gene polymorphism as a severity factor in systemic lupus erythematosus", Arthrits and Rheumatism, 37(9):1380-1385 (1994).
Blakemore et al., Interleukin 1 receptor antagonist gene polymorphism as a severity factor in systemic lupus erythematosus , Arthrits and Rheumatism , 37(9):1380 1385 (1994). *
Clark et al., "Genomic sequence for human prointerleukin 1 beta: possible evolution from a reverse transcribed prointerleukin 1 alpha gene", Nucl Acids Res, 14:7897-7914 (1986).
Clark et al., Genomic sequence for human prointerleukin 1 beta: possible evolution from a reverse transcribed prointerleukin 1 alpha gene , Nucl Acids Res , 14:7897 7914 (1986). *
Clay et al., Hum. Genet. 94, 407 410 (1994). *
Clay et al., Hum. Genet. 94, 407-410 (1994).
Clay et al., Hum. Genet. 97, 723 726 (1996). *
Clay et al., Hum. Genet. 97, 723-726 (1996).
Dequeker et al., "Genetic determinants of bone mineral content content at the spine and radius: A twin study", Bone, 8:207-209 (1987).
Dequeker et al., Genetic determinants of bone mineral content content at the spine and radius: A twin study , Bone , 8:207 209 (1987). *
di Giovine, et al., "Single base polymorphism at -511 in the human interleukin-1β gene (IL-1β)", Human Molecular Genetics, 1(6):450 (1992).
di Giovine, et al., Single base polymorphism at 511 in the human interleukin 1 gene (IL 1 ) , Human Molecular Genetics , 1(6):450 (1992). *
Duff, "Cytokines and anti-cytokines", Br. J. Rheumatol, 32 (Suppl 1):15-20 (1993).
Duff, Cytokines and anti cytokines , Br. J. Rheumatol , 32 (Suppl 1):15 20 (1993). *
Eastell and Riggs, "Diagnostic evaluation of osteoporosis", Endocrinol Metab Clin North Am, 17(3):547-71 (1988).
Eastell and Riggs, "New approaches to the treatment of osteoporosis", Clin Obstet Gynecol, 30(4):860-70 (1987a).
Eastell and Riggs, "Treatment of osteoporosis", Obstet Gynecol Clin North AM, 14(1):77-88 (1987b).
Eastell and Riggs, Diagnostic evaluation of osteoporosis , Endocrinol Metab Clin North Am , 17(3):547 71 (1988). *
Eastell and Riggs, New approaches to the treatment of osteoporosis , Clin Obstet Gynecol , 30(4):860 70 (1987a). *
Eastell and Riggs, Treatment of osteoporosis , Obstet Gynecol Clin North AM , 14(1):77 88 (1987b). *
Eastell, "Management of corticosteroid-induced osteoporosis: UK Consensus Group Meeting on Osteoporosis", J Intern Med, 23(5):439-47 (1995).
Eastell, Management of corticosteroid induced osteoporosis: UK Consensus Group Meeting on Osteoporosis , J Intern Med , 23(5):439 47 (1995). *
Furutani et al., "Complete nucleotide sequence of the gene for human interleukin 1 alpha", Nucl Acids Res, 14:3167-319 (1986).
Furutani et al., Complete nucleotide sequence of the gene for human interleukin 1 alpha , Nucl Acids Res , 14:3167 319 (1986). *
Garabedian, "Genetic aspects of osteoporosis", Curr Opin Rheumatol, 7(3):237-9 (1995).
Garabedian, Genetic aspects of osteoporosis , Curr Opin Rheumatol , 7(3):237 9 (1995). *
Kanis et al., "The diagnosis of osteoporosis", J Bone Miner Res, 10(6):978-84 (1995).
Kanis et al., The diagnosis of osteoporosis , J Bone Miner Res , 10(6):978 84 (1995). *
Kelly et al., "Genetic influences on bone turnover, bone density and fracture", Eur J Endocrinol, 133(3):265-71 (1995).
Kelly et al., Genetic influences on bone turnover, bone density and fracture , Eur J Endocrinol , 133(3):265 71 (1995). *
Krall et al., "Vitamin D receptor alleles and rates of bone loss: influences of years since menopause and calcium intake", J Bone Miner Res, 10(6):978-84 (1995).
Krall et al., Vitamin D receptor alleles and rates of bone loss: influences of years since menopause and calcium intake , J Bone Miner Res , 10(6):978 84 (1995). *
Mansfield et al., "Novel genetic association between ulcerative colitis and the anti-inflammatory cytokine interleukin 1 receptor antagonist", Gastroenterology, 106:637-642 (1994).
Mansfield et al., Novel genetic association between ulcerative colitis and the anti inflammatory cytokine interleukin 1 receptor antagonist , Gastroenterology , 106:637 642 (1994). *
Matfin, "The role of cytokines in normal and pathological bone states", Br J Hosp Med, 49(6):407, 410-5 (1993).
Matfin, The role of cytokines in normal and pathological bone states , Br J Hosp Med , 49(6):407, 410 5 (1993). *
McDowell, T.L. et al., "A genetic association between juvenile rheumatoid arthritis and a novel interleukin-1 alpha polymorphism", Arthritis Rheum, 38:221-228 (1995).
McDowell, T.L. et al., A genetic association between juvenile rheumatoid arthritis and a novel interleukin 1 alpha polymorphism , Arthritis Rheum , 38:221 228 (1995). *
McGuire et al., "Variation in the TNF-∝ promoter region associated with susceptibility to cerebral malaria", Nature, 371:508-511 (1994).
McGuire et al., Variation in the TNF promoter region associated with susceptibility to cerebral malaria , Nature , 371:508 511 (1994). *
Mundy, "Cytokines and growth factors in the regulation of bone remodeling", J Bone Miner Res, 8(suppl 2):S505-10 (1993).
Mundy, Cytokines and growth factors in the regulation of bone remodeling , J Bone Miner Res , 8(suppl 2):S505 10 (1993). *
Peel and Eastell, "ABC of rheumatology. OSteoporosis", BMJ, 310(6985):989-92 (1995).
Peel and Eastell, "Diagnostic value of estimated volumetric bone mineral density of the lumbar spine in osteoporosis", J Bone Miner Res, 9(3):317-20 (1994).
Peel and Eastell, "Measurement of bone mass and turnover", Baillieres Clin Rheumatol, 7(3):479-98 (1993).
Peel and Eastell, ABC of rheumatology. OSteoporosis , BMJ, 310(6985):989 92 (1995). *
Peel and Eastell, Diagnostic value of estimated volumetric bone mineral density of the lumbar spine in osteoporosis , J Bone Miner Res , 9(3):317 20 (1994). *
Peel and Eastell, Measurement of bone mass and turnover , Baillieres Clin Rheumatol , 7(3):479 98 (1993). *
Pocock et al., "Genetic determinants of bone mass in adults. A twin study.", J Clin Invest, 80:706-710 (1987).
Pocock et al., Genetic determinants of bone mass in adults. A twin study. , J Clin Invest , 80:706 710 (1987). *
Poli et al., "Interleukin-6 deficient mice are protected from bone loss caused by estrogen depletion", EMBO J, 13(5):1189-96 (1994).
Poli et al., Interleukin 6 deficient mice are protected from bone loss caused by estrogen depletion , EMBO J , 13(5):1189 96 (1994). *
Prockop and Kivirikko, "Collagens: molecular biology, diseases and potentials for therapy", Annu Rev Biochem, 64:403-34 (1995).
Prockop and Kivirikko, Collagens: molecular biology, diseases and potentials for therapy , Annu Rev Biochem , 64:403 34 (1995). *
Rickard et al., "Proliferative responses to estradiol, 1L-1α and TGFβ by cells expressing alkaline phosphatase in human osteoblast-like cell cultures", Calcif Tissue Int, 52(3):227-33 (1993).
Rickard et al., Proliferative responses to estradiol, 1L 1 and TGF by cells expressing alkaline phosphatase in human osteoblast like cell cultures , Calcif Tissue Int , 52(3):227 33 (1993). *
Sambrook et al., "Genetics of osteoporosis", Br J Rheumatol, 33(11):1007-11 (1994).
Sambrook et al., Genetics of osteoporosis , Br J Rheumatol , 33(11):1007 11 (1994). *
Slemenda et al., "Long-term bone loss in men: effects of genetic and environmental factors", Ann Intern Med, 117:286-291 (1992).
Slemenda et al., Long term bone loss in men: effects of genetic and environmental factors , Ann Intern Med , 117:286 291 (1992). *
Smith et al., "Genetic factors in determining bone mass", J Clin Invest, 52:2800-2808 (1973).
Smith et al., Genetic factors in determining bone mass , J Clin Invest , 52:2800 2808 (1973). *
Tarlow et al., "Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 89-bp tandem repeat", Human Genetics, 91:403-404 (1993).
Tarlow et al., J. Inv. Dermatol. 103, 387 390 (1994). *
Tarlow et al., J. Inv. Dermatol. 103, 387-390 (1994).
Tarlow et al., Polymorphism in human IL 1 receptor antagonist gene intron 2 is caused by variable numbers of an 89 bp tandem repeat , Human Genetics , 91:403 404 (1993). *
Teegarden et al., "Peak bone mass in young women", J Bone Miner Res, 10(5):711-5 (1995).
Teegarden et al., Peak bone mass in young women , J Bone Miner Res , 10(5):711 5 (1995). *
Tokita et al., "Genetic influences on type I collagen synthesis and degradation: further evidence for genetic regulation of bone turnover", J Clin Endocrinol Metabol, 78(6):1461-6 (1994).
Tokita et al., Genetic influences on type I collagen synthesis and degradation: further evidence for genetic regulation of bone turnover , J Clin Endocrinol Metabol , 78(6):1461 6 (1994). *
Verjans et al., "Polymorphism of the tumor necrosis factor region in relation to disease: An overview", Rheum Dis Clin North Am, 18:177-186 (1992).
Verjans et al., Polymorphism of the tumor necrosis factor region in relation to disease: An overview , Rheum Dis Clin North Am , 18:177 186 (1992). *
Wilson et al., "Single based polymorphism in the human Tumor Necrosis Factor alpha (TNFα) gene detectable by Nco1 restriction of PCR product", Human Molecular Genetics 1, No. 5:353 (1992).
Wilson et al., Single based polymorphism in the human Tumor Necrosis Factor alpha (TNF ) gene detectable by Nco1 restriction of PCR product , Human Molecular Genetics 1 , No. 5:353 (1992). *

Cited By (51)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5998137A (en) * 1996-01-17 1999-12-07 Grainger; David J. Methods of diagnosis by detecting polymorphisms in the TGF-β1 promoter
US5939260A (en) * 1996-04-19 1999-08-17 Gemini International Holdings Limited Methods of diagnosing a predisposition for osteoarthritis via detection of vitamin D receptor gene polymorphisms
US6713253B1 (en) 1996-10-10 2004-03-30 Interleukin Genetics, Inc. Detecting genetic predisposition to sight-threatening diabetic retinopathy
US7820383B2 (en) 1997-03-10 2010-10-26 Interleukin Genetics, Inc. Method for diagnosing myocardial infarction
US20040229264A1 (en) * 1997-03-10 2004-11-18 Interleukin Genetics, Inc. Diagnostics and therapeutics for restenosis
US6210877B1 (en) 1997-03-10 2001-04-03 Interleukin Genetics, Inc. Prediction of coronary artery disease
US20030175764A1 (en) * 1997-03-10 2003-09-18 Interleukin Genetics, Inc. Diagnostics and therapeutics for cardiovascular disease
WO1998040517A1 (en) * 1997-03-10 1998-09-17 Medical Science Systems, Inc. Prediction of coronary artery disease
US6524795B1 (en) * 1997-03-10 2003-02-25 Interleukin Genetics, Inc. Diagnostics for cardiovascular disorders
US6391543B2 (en) * 1997-04-23 2002-05-21 Abbott Laboratories Reagents and methods useful for detecting diseases of the prostate
US20020086316A1 (en) * 1997-04-23 2002-07-04 Billing-Medel Patricia A. Reagents and methods useful for detecting diseases of the prostate
US6706478B2 (en) * 1997-05-29 2004-03-16 Interleukin Genetics, Inc. Diagnostics and therapeutics for diseases associated with an IL-1 inflammatory haplotype
US20050282198A1 (en) * 1997-05-29 2005-12-22 Interleukin Genetics, Inc. Diagnostics and therapeutics for diseases associated with an IL-1 inflammatory haplotype
US20040152124A1 (en) * 1997-05-29 2004-08-05 Duff Gordon W. Diagnostics and therapeutics for diseases associated with an IL-1 inflammatory haplotype
US6268142B1 (en) * 1997-05-29 2001-07-31 Interleukin Genetics, Inc. Diagnostics and therapeutics for diseases associated with an IL-1 inflammatory haplotype
US20050032077A1 (en) * 1998-03-10 2005-02-10 Duff Gordon W. Detecting genetic predisposition to sight-threatening diabetic retinopathy
US6733967B1 (en) 1998-04-21 2004-05-11 Interleukin Genetics, Inc. Fetal testing for prediction of low birth weight
US6762023B1 (en) 1998-11-30 2004-07-13 Drexel University Methods for identifying individuals at risk of developing osteoporosis
WO2000032826A1 (en) * 1998-11-30 2000-06-08 Drexel University Methods and kits for identifying individuals at risk of developing osteoporosis
EP2071040A2 (de) 1999-05-26 2009-06-17 Medical Science System, Inc. Diagnostika und Therapeutika für Gefäßerkrankungen
US20050064453A1 (en) * 1999-06-30 2005-03-24 Gordon Duff Diagnostics and therapeutics for early-onset menopause
US20040110168A1 (en) * 1999-08-30 2004-06-10 Interleukin Genetics, Inc. Diagnostics and therapeutics for osteoporosis
US20090023147A1 (en) * 1999-08-30 2009-01-22 Kenneth Kornman Diagnostics and therapeutics for osteoporosis
US6558905B1 (en) * 1999-08-30 2003-05-06 Interleukin Genetics, Inc. Diagnostics and therapeutics for osteoporosis
US20030124524A1 (en) * 2000-06-23 2003-07-03 Kenneth Kornman Screening assays for identifying modulators of the inflammatory or immune response
US7723028B2 (en) 2000-08-30 2010-05-25 Interleukin Genetics, Inc. Diagnostics and therapeutics for osteoporosis
US20050084882A1 (en) * 2000-08-30 2005-04-21 Kenneth Kormman Diagnostics and therapeutics for osteoporosis
US20030152947A1 (en) * 2001-06-15 2003-08-14 Crossman David C. Methods for detecting and treating the early onset of aging-related conditions
US20080199865A1 (en) * 2001-06-15 2008-08-21 Crossman David C Methods for Detecting and Treating the Early Onset of Aging-Related Conditions
US20050221306A1 (en) * 2001-11-03 2005-10-06 Wilson Scott G Detection of predisposition to osteoporosis
US20080311581A1 (en) * 2001-11-19 2008-12-18 David Wyllie Functional polymorphisms of the interleukin-1 locus affecting transcription and susceptibility to inflammatory and infectious diseases
US20030235890A1 (en) * 2001-11-19 2003-12-25 David Wyllie Functional polymorphisms of the interleukin-1 locus affecting transcription and susceptibility to inflammatory and infectious diseases
US20030148288A1 (en) * 2002-02-01 2003-08-07 Yi-Wei Tang Colorimetric genetic test for clinically significant TNF polymorphism and methods of use thereof
US20030198316A1 (en) * 2002-04-17 2003-10-23 Piet Dewaele Osteoporosis screening method
US20040229228A1 (en) * 2002-07-25 2004-11-18 Northwestern University Il-1 genotype in early kidney allograft rejection
WO2004065630A1 (en) * 2003-01-24 2004-08-05 King's College London Detection of predisposition to osteoporosis
US20090191564A1 (en) * 2005-11-17 2009-07-30 Sheila Francis Diagnostics and therapeutics for cardiovascular disorders
US20090170105A1 (en) * 2007-11-08 2009-07-02 Interleukin Genetics, Inc. Diagnostics for Aging-Related Dermatologic Disorders
US20100129798A1 (en) * 2008-05-02 2010-05-27 Interleukin Genetics, Inc. Detecting genetic predisposition to osteoarthritis associated conditions
US20100098775A1 (en) * 2008-05-02 2010-04-22 Interleukin Genetics, Inc. Detecting genetic predisposition to osteoarthritis associated conditions
EP3059323A1 (de) 2008-05-02 2016-08-24 Interleukin Genetics, Inc. Nachweis von genetischer veranlagung für osteoarthritische erkrankungen
EP3467126A1 (de) 2008-05-02 2019-04-10 Orig3n, Inc. Nachweis von genetischer veranlagung für osteoarthritische erkrankungen
WO2017123696A1 (en) 2016-01-12 2017-07-20 Interleukin Genetics, Inc. Methods for predicting response to treatment
US10894985B2 (en) 2016-01-12 2021-01-19 Sitokine Limited Methods for predicting response to treatment
WO2018130670A1 (en) 2017-01-12 2018-07-19 Cardioforecast Ltd Methods and kits for treating cardiovascular disease
US10329620B2 (en) 2017-01-12 2019-06-25 Cardioforecast Ltd. Methods and kits for treating cardiovascular disease
US10337070B2 (en) 2017-01-12 2019-07-02 Cardioforecast Ltd. Methods and kits for treating cardiovascular disease
US11486006B2 (en) 2017-01-12 2022-11-01 Sitokine Limited Methods and kits for treating cardiovascular disease
WO2020245402A1 (en) 2019-06-06 2020-12-10 Cardioforecast Ltd Compositions and methods for treating lung, colorectal and breast cancer
WO2021028469A1 (en) 2019-08-12 2021-02-18 Sitokine Limited Compositions and methods for treating cytokine release syndrome and neurotoxicity
WO2021205013A1 (en) 2020-04-09 2021-10-14 Sitokine Limited Compositions and methods for treating covid-19

Also Published As

Publication number Publication date
NZ329530A (en) 1999-10-28
DE69724209T2 (de) 2004-06-17
AU2607797A (en) 1997-10-29
AU712461B2 (en) 1999-11-04
EP0832298A1 (de) 1998-04-01
WO1997038135A1 (en) 1997-10-16
DE69724209D1 (de) 2003-09-25
CN100347313C (zh) 2007-11-07
ES2208892T3 (es) 2004-06-16
CA2226223C (en) 2001-11-20
CN1194668A (zh) 1998-09-30
ATE247718T1 (de) 2003-09-15
EP0832298B1 (de) 2003-08-20
IL122808A0 (en) 1998-08-16
EP0832298A4 (de) 1999-09-08
MX9800192A (es) 1998-11-30
IL122808A (en) 2000-08-31
CA2226223A1 (en) 1997-10-16
ZA972909B (en) 1998-10-26

Similar Documents

Publication Publication Date Title
US5698399A (en) Detecting genetic predisposition for osteoporosis
Cantagrel et al. Interleukin‐1β, interleukin‐1 receptor antagonist, interleukin‐4, and interleukin‐10 gene polymorphisms: Relationship to occurrence and severity of rheumatoid arthritis
JP4042811B2 (ja) 歯周疾患の遺伝的素質の検出
Genevay et al. Association of interleukin‐4 and interleukin‐1B gene variants with Larsen score progression in rheumatoid arthritis
Horton Jr et al. An association between an aggrecan polymorphic allele and bilateral hand osteoarthritis in elderly white men: data from the Baltimore Longitudinal Study of Aging (BLSA)
Takacs et al. Sib pair linkage and association studies between bone mineral density and the interleukin-6 gene locus
AU2004263184B2 (en) Diagnostic and therapeutics for osteoporosis
AU718326B2 (en) Determination of collagen genotype
US20090023147A1 (en) Diagnostics and therapeutics for osteoporosis
EP2993238A1 (de) Prognose der reaktion auf eine behandlung mit anti-tnf-alpha bei patienten mit rheumatoider arthritis
Marc et al. Association of vitamin D receptor gene polymorphism with bone mineral density in Slovenian postmenopausal women
AU727077B2 (en) Diagnostic method and apparatus based on polymorphism in an IL-6 gene
Toussirot et al. The association of HLA-DM genes with rheumatoid arthritis in Eastern France
US6803197B1 (en) Method for determining susceptibility to bone damage by screening polymorphisms in the vitamin D receptor gene
EP1112384A1 (de) Methode zur bestimmung der veranlagung zu herzkrankheiten mittels prüfung von polymorphismen im vitamin d rezeptor gen
Han et al. Nonassociation of interleukin-1 receptor antagonist genotypes with bone mineral density, bone turnover status, and estrogen responsiveness in Korean postmenopausal women
Raafat et al. Tumor necrosis factor-α: molecular assessment of gene expression, genetic variants and serum level in Egyptian patients with knee osteoarthritis
WO1993011149A1 (en) Methods of detecting a genetic predisposition for osteoporosis
MXPA98007040A (en) Determination of the collage genotype

Legal Events

Date Code Title Description
STCF Information on status: patent grant

Free format text: PATENTED CASE

AS Assignment

Owner name: MEDICAL SCIENCE SYSTEMS, INC., CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:SHEFFIELD, UNIVERSITY OF THE;REEL/FRAME:008847/0610

Effective date: 19971111

AS Assignment

Owner name: SHEFFIELD, UNIVERSITY OF, THE, UNITED KINGDOM

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:DUFF, GORDON W.;RUSSELL, GRAHAM;EASTELL, RICHARD;REEL/FRAME:009360/0194

Effective date: 19971013

AS Assignment

Owner name: INTERLEUKIN GENETICS, INC., TEXAS

Free format text: CHANGE OF NAME;ASSIGNOR:MEDICAL SCIENCE SYSTEMS, INC;REEL/FRAME:010371/0858

Effective date: 19990820

FPAY Fee payment

Year of fee payment: 4

AS Assignment

Owner name: PYXIS INNOVATIONS INC., MICHIGAN

Free format text: SECURITY AGREEMENT;ASSIGNOR:INTERLEUKIN GENETICS, INC.;REEL/FRAME:013193/0257

Effective date: 20021023

FEPP Fee payment procedure

Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: SMALL ENTITY

FPAY Fee payment

Year of fee payment: 8

FPAY Fee payment

Year of fee payment: 12